SARS coronavirus papain-like protease induces Egr-1-dependent up-regulation of TGF-β1 via ROS/p38 MAPK/STAT3 pathway.
Identifieur interne : 000F48 ( Main/Exploration ); précédent : 000F47; suivant : 000F49SARS coronavirus papain-like protease induces Egr-1-dependent up-regulation of TGF-β1 via ROS/p38 MAPK/STAT3 pathway.
Auteurs : Shih-Wein Li [Taïwan] ; Ching-Ying Wang [Taïwan] ; Yu-Jen Jou [Taïwan] ; Tsuey-Ching Yang [Taïwan] ; Su-Hua Huang [Taïwan] ; Lei Wan [Taïwan] ; Ying-Ju Lin [Taïwan] ; Cheng-Wen Lin [Taïwan]Source :
- Scientific reports [ 2045-2322 ] ; 2016.
Descripteurs français
- KwdFr :
- ARN messager (génétique), ARN messager (métabolisme), Animaux, Cellules A549, Cellules épithéliales (métabolisme), Espèces réactives de l'oxygène (métabolisme), Extinction de l'expression des gènes (), Facteur de croissance transformant bêta-1 (biosynthèse), Facteur de croissance transformant bêta-1 (génétique), Facteur de croissance transformant bêta-1 (métabolisme), Facteur de transcription EGR-1 (métabolisme), Facteur de transcription NF-kappa B (métabolisme), Facteur de transcription STAT-3 (métabolisme), Facteur de transcription Sp1 (métabolisme), Fibrose, Humains, Modèles animaux de maladie humaine, Modèles biologiques, Papaïne (pharmacologie), Petit ARN interférent (métabolisme), Poumon (cytologie), Protéine gliofibrillaire acide (métabolisme), Régions promotrices (génétique) (génétique), Régulation positive (), Souris de lignée BALB C, Thrombospondine-1 (métabolisme), Transduction du signal (), Vimentine (métabolisme), Virus du SRAS (enzymologie), p38 Mitogen-Activated Protein Kinases (métabolisme).
- MESH :
- biosynthèse : Facteur de croissance transformant bêta-1.
- cytologie : Poumon.
- enzymologie : Virus du SRAS.
- génétique : ARN messager, Facteur de croissance transformant bêta-1, Régions promotrices (génétique).
- métabolisme : ARN messager, Cellules épithéliales, Espèces réactives de l'oxygène, Facteur de croissance transformant bêta-1, Facteur de transcription EGR-1, Facteur de transcription NF-kappa B, Facteur de transcription STAT-3, Facteur de transcription Sp1, Petit ARN interférent, Protéine gliofibrillaire acide, Thrombospondine-1, Vimentine, p38 Mitogen-Activated Protein Kinases.
- pharmacologie : Papaïne.
- Animaux, Cellules A549, Extinction de l'expression des gènes, Fibrose, Humains, Modèles animaux de maladie humaine, Modèles biologiques, Régulation positive, Souris de lignée BALB C, Transduction du signal.
English descriptors
- KwdEn :
- A549 Cells, Animals, Disease Models, Animal, Early Growth Response Protein 1 (metabolism), Epithelial Cells (metabolism), Fibrosis, Gene Silencing (drug effects), Glial Fibrillary Acidic Protein (metabolism), Humans, Lung (cytology), Mice, Inbred BALB C, Models, Biological, NF-kappa B (metabolism), Papain (pharmacology), Promoter Regions, Genetic (genetics), RNA, Messenger (genetics), RNA, Messenger (metabolism), RNA, Small Interfering (metabolism), Reactive Oxygen Species (metabolism), SARS Virus (enzymology), STAT3 Transcription Factor (metabolism), Signal Transduction (drug effects), Sp1 Transcription Factor (metabolism), Thrombospondin 1 (metabolism), Transforming Growth Factor beta1 (biosynthesis), Transforming Growth Factor beta1 (genetics), Transforming Growth Factor beta1 (metabolism), Up-Regulation (drug effects), Vimentin (metabolism), p38 Mitogen-Activated Protein Kinases (metabolism).
- MESH :
- chemical , biosynthesis : Transforming Growth Factor beta1.
- chemical , genetics : RNA, Messenger, Transforming Growth Factor beta1.
- chemical , metabolism : Early Growth Response Protein 1, Glial Fibrillary Acidic Protein, NF-kappa B, RNA, Messenger, RNA, Small Interfering, Reactive Oxygen Species, STAT3 Transcription Factor, Sp1 Transcription Factor, Thrombospondin 1, Transforming Growth Factor beta1, Vimentin, p38 Mitogen-Activated Protein Kinases.
- cytology : Lung.
- drug effects : Gene Silencing, Signal Transduction, Up-Regulation.
- enzymology : SARS Virus.
- genetics : Promoter Regions, Genetic.
- metabolism : Epithelial Cells.
- chemical , pharmacology : Papain.
- A549 Cells, Animals, Disease Models, Animal, Fibrosis, Humans, Mice, Inbred BALB C, Models, Biological.
Abstract
SARS coronavirus (SARS-CoV) papain-like protease (PLpro) has been identified in TGF-β1 up-regulation in human promonocytes (Proteomics 2012, 12: 3193-205). This study investigates the mechanisms of SARS-CoV PLpro-induced TGF-β1 promoter activation in human lung epithelial cells and mouse models. SARS-CoV PLpro dose- and time-dependently up-regulates TGF-β1 and vimentin in A549 cells. Dual luciferase reporter assays with TGF-β1 promoter plasmids indicated that TGF-β1 promoter region between -175 to -60, the Egr-1 binding site, was responsible for TGF-β1 promoter activation induced by SARS-CoV PLpro. Subcellular localization analysis of transcription factors showed PLpro triggering nuclear translocation of Egr-1, but not NF-κB and Sp-1. Meanwhile, Egr-1 silencing by siRNA significantly reduced PLpro-induced up-regulation of TGF-β1, TSP-1 and pro-fibrotic genes. Furthermore, the inhibitors for ROS (YCG063), p38 MAPK (SB203580), and STAT3 (Stattic) revealed ROS/p38 MAPK/STAT3 pathway involving in Egr-1 dependent activation of TGF-β1 promoter induced by PLpro. In a mouse model with a direct pulmonary injection, PLpro stimulated macrophage infiltration into lung, up-regulating Egr-1, TSP-1, TGF-β1 and vimentin expression in lung tissues. The results revealed that SARS-CoV PLpro significantly triggered Egr-1 dependent activation of TGF-β1 promoter via ROS/p38 MAPK/STAT3 pathway, correlating with up-regulation of pro-fibrotic responses in vitro and in vivo.
DOI: 10.1038/srep25754
PubMed: 27173006
Affiliations:
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Taichung</wicri:regionArea><wicri:noRegion>Taichung</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Ching Ying" sort="Wang, Ching Ying" uniqKey="Wang C" first="Ching-Ying" last="Wang">Ching-Ying Wang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan.</nlm:affiliation><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung</wicri:regionArea><wicri:noRegion>Taichung</wicri:noRegion></affiliation></author><author><name sortKey="Jou, Yu Jen" sort="Jou, Yu Jen" uniqKey="Jou Y" first="Yu-Jen" last="Jou">Yu-Jen Jou</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan.</nlm:affiliation><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung</wicri:regionArea><wicri:noRegion>Taichung</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Tsuey Ching" sort="Yang, Tsuey Ching" uniqKey="Yang T" first="Tsuey-Ching" last="Yang">Tsuey-Ching Yang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biotechnology and Laboratory Science in Medicine, National Yang Ming University, Taipei, Taiwan.</nlm:affiliation><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Biotechnology and Laboratory Science in Medicine, National Yang Ming University, Taipei</wicri:regionArea><wicri:noRegion>Taipei</wicri:noRegion></affiliation></author><author><name sortKey="Huang, Su Hua" sort="Huang, Su Hua" uniqKey="Huang S" first="Su-Hua" last="Huang">Su-Hua Huang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biotechnology, Asia University, Wufeng, Taichung, Taiwan.</nlm:affiliation><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Biotechnology, Asia University, Wufeng, Taichung</wicri:regionArea><wicri:noRegion>Taichung</wicri:noRegion></affiliation></author><author><name sortKey="Wan, Lei" sort="Wan, Lei" uniqKey="Wan L" first="Lei" last="Wan">Lei Wan</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung, Taiwan.</nlm:affiliation><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung</wicri:regionArea><wicri:noRegion>Taichung</wicri:noRegion></affiliation></author><author><name sortKey="Lin, Ying Ju" sort="Lin, Ying Ju" uniqKey="Lin Y" first="Ying-Ju" last="Lin">Ying-Ju Lin</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung, Taiwan.</nlm:affiliation><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung</wicri:regionArea><wicri:noRegion>Taichung</wicri:noRegion></affiliation></author><author><name sortKey="Lin, Cheng Wen" sort="Lin, Cheng Wen" uniqKey="Lin C" first="Cheng-Wen" last="Lin">Cheng-Wen Lin</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan.</nlm:affiliation><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung</wicri:regionArea><wicri:noRegion>Taichung</wicri:noRegion></affiliation></author></analytic><series><title level="j">Scientific reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>A549 Cells</term><term>Animals</term><term>Disease Models, Animal</term><term>Early Growth Response Protein 1 (metabolism)</term><term>Epithelial Cells (metabolism)</term><term>Fibrosis</term><term>Gene Silencing (drug effects)</term><term>Glial Fibrillary Acidic Protein (metabolism)</term><term>Humans</term><term>Lung (cytology)</term><term>Mice, Inbred BALB C</term><term>Models, Biological</term><term>NF-kappa B (metabolism)</term><term>Papain (pharmacology)</term><term>Promoter Regions, Genetic (genetics)</term><term>RNA, Messenger (genetics)</term><term>RNA, Messenger (metabolism)</term><term>RNA, Small Interfering (metabolism)</term><term>Reactive Oxygen Species (metabolism)</term><term>SARS Virus (enzymology)</term><term>STAT3 Transcription Factor (metabolism)</term><term>Signal Transduction (drug effects)</term><term>Sp1 Transcription Factor (metabolism)</term><term>Thrombospondin 1 (metabolism)</term><term>Transforming Growth Factor beta1 (biosynthesis)</term><term>Transforming Growth Factor beta1 (genetics)</term><term>Transforming Growth Factor beta1 (metabolism)</term><term>Up-Regulation (drug effects)</term><term>Vimentin (metabolism)</term><term>p38 Mitogen-Activated Protein Kinases (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN messager (génétique)</term><term>ARN messager (métabolisme)</term><term>Animaux</term><term>Cellules A549</term><term>Cellules épithéliales (métabolisme)</term><term>Espèces réactives de l'oxygène (métabolisme)</term><term>Extinction de l'expression des gènes ()</term><term>Facteur de croissance transformant bêta-1 (biosynthèse)</term><term>Facteur de croissance transformant bêta-1 (génétique)</term><term>Facteur de croissance transformant bêta-1 (métabolisme)</term><term>Facteur de transcription EGR-1 (métabolisme)</term><term>Facteur de transcription NF-kappa B (métabolisme)</term><term>Facteur de transcription STAT-3 (métabolisme)</term><term>Facteur de transcription Sp1 (métabolisme)</term><term>Fibrose</term><term>Humains</term><term>Modèles animaux de maladie humaine</term><term>Modèles biologiques</term><term>Papaïne (pharmacologie)</term><term>Petit ARN interférent (métabolisme)</term><term>Poumon (cytologie)</term><term>Protéine gliofibrillaire acide (métabolisme)</term><term>Régions promotrices (génétique) (génétique)</term><term>Régulation positive ()</term><term>Souris de lignée BALB C</term><term>Thrombospondine-1 (métabolisme)</term><term>Transduction du signal ()</term><term>Vimentine (métabolisme)</term><term>Virus du SRAS (enzymologie)</term><term>p38 Mitogen-Activated Protein Kinases (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Transforming Growth Factor beta1</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>RNA, Messenger</term><term>Transforming Growth Factor beta1</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Early Growth Response Protein 1</term><term>Glial Fibrillary Acidic Protein</term><term>NF-kappa B</term><term>RNA, Messenger</term><term>RNA, Small Interfering</term><term>Reactive Oxygen Species</term><term>STAT3 Transcription Factor</term><term>Sp1 Transcription Factor</term><term>Thrombospondin 1</term><term>Transforming Growth Factor beta1</term><term>Vimentin</term><term>p38 Mitogen-Activated Protein Kinases</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Facteur de croissance transformant bêta-1</term></keywords><keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Lung</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Gene Silencing</term><term>Signal Transduction</term><term>Up-Regulation</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Promoter Regions, Genetic</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>ARN messager</term><term>Facteur de croissance transformant bêta-1</term><term>Régions promotrices (génétique)</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Epithelial Cells</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>ARN messager</term><term>Cellules épithéliales</term><term>Espèces réactives de l'oxygène</term><term>Facteur de croissance transformant bêta-1</term><term>Facteur de transcription EGR-1</term><term>Facteur de transcription NF-kappa B</term><term>Facteur de transcription STAT-3</term><term>Facteur de transcription Sp1</term><term>Petit ARN interférent</term><term>Protéine gliofibrillaire acide</term><term>Thrombospondine-1</term><term>Vimentine</term><term>p38 Mitogen-Activated Protein Kinases</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Papaïne</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Papain</term></keywords><keywords scheme="MESH" xml:lang="en"><term>A549 Cells</term><term>Animals</term><term>Disease Models, Animal</term><term>Fibrosis</term><term>Humans</term><term>Mice, Inbred BALB C</term><term>Models, Biological</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules A549</term><term>Extinction de l'expression des gènes</term><term>Fibrose</term><term>Humains</term><term>Modèles animaux de maladie humaine</term><term>Modèles biologiques</term><term>Régulation positive</term><term>Souris de lignée BALB C</term><term>Transduction du signal</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">SARS coronavirus (SARS-CoV) papain-like protease (PLpro) has been identified in TGF-β1 up-regulation in human promonocytes (Proteomics 2012, 12: 3193-205). This study investigates the mechanisms of SARS-CoV PLpro-induced TGF-β1 promoter activation in human lung epithelial cells and mouse models. SARS-CoV PLpro dose- and time-dependently up-regulates TGF-β1 and vimentin in A549 cells. Dual luciferase reporter assays with TGF-β1 promoter plasmids indicated that TGF-β1 promoter region between -175 to -60, the Egr-1 binding site, was responsible for TGF-β1 promoter activation induced by SARS-CoV PLpro. Subcellular localization analysis of transcription factors showed PLpro triggering nuclear translocation of Egr-1, but not NF-κB and Sp-1. Meanwhile, Egr-1 silencing by siRNA significantly reduced PLpro-induced up-regulation of TGF-β1, TSP-1 and pro-fibrotic genes. Furthermore, the inhibitors for ROS (YCG063), p38 MAPK (SB203580), and STAT3 (Stattic) revealed ROS/p38 MAPK/STAT3 pathway involving in Egr-1 dependent activation of TGF-β1 promoter induced by PLpro. In a mouse model with a direct pulmonary injection, PLpro stimulated macrophage infiltration into lung, up-regulating Egr-1, TSP-1, TGF-β1 and vimentin expression in lung tissues. The results revealed that SARS-CoV PLpro significantly triggered Egr-1 dependent activation of TGF-β1 promoter via ROS/p38 MAPK/STAT3 pathway, correlating with up-regulation of pro-fibrotic responses in vitro and in vivo.</div></front></TEI><affiliations><list><country><li>Taïwan</li></country></list><tree><country name="Taïwan"><noRegion><name sortKey="Li, Shih Wein" sort="Li, Shih Wein" uniqKey="Li S" first="Shih-Wein" last="Li">Shih-Wein Li</name></noRegion><name sortKey="Huang, Su Hua" sort="Huang, Su Hua" uniqKey="Huang S" first="Su-Hua" last="Huang">Su-Hua Huang</name><name sortKey="Jou, Yu Jen" sort="Jou, Yu Jen" uniqKey="Jou Y" first="Yu-Jen" last="Jou">Yu-Jen Jou</name><name sortKey="Lin, Cheng Wen" sort="Lin, Cheng Wen" uniqKey="Lin C" first="Cheng-Wen" last="Lin">Cheng-Wen Lin</name><name sortKey="Lin, Ying Ju" sort="Lin, Ying Ju" uniqKey="Lin Y" first="Ying-Ju" last="Lin">Ying-Ju Lin</name><name sortKey="Wan, Lei" sort="Wan, Lei" uniqKey="Wan L" first="Lei" last="Wan">Lei Wan</name><name sortKey="Wang, Ching Ying" sort="Wang, Ching Ying" uniqKey="Wang C" first="Ching-Ying" last="Wang">Ching-Ying Wang</name><name sortKey="Yang, Tsuey Ching" sort="Yang, Tsuey Ching" uniqKey="Yang T" first="Tsuey-Ching" last="Yang">Tsuey-Ching Yang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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